83 Concomitance of primary systemic lupus erythematosus and Wilson’s disease in a male child: a case report

Abstract Background Wilson’s disease (WD) is a rare, recessively inherited disorder of copper metabolism with its accumulation in multiple organs particularly in the liver and brain. Systematic lupus erythematosus (SLE) is an autoimmune disease like Wilson’s disease, involves multiple organs and systems. The combination of Wilson's disease and systemic lupus erythematosus (SLE) is not usual apart from iatrogenism. Objectives we present a pediatric case of concurrent Wilson’s disease and primary SLE not induced by penicillamine. After extensive research in the literature, this is the only male case described so far. The other seven cases reported are female. Case presentation A previously well 12-year-old boy was admitted to University Hospital Center of Batna (Algeria) with acute haemolysis (pallor, subictereus, and red urine). There was no consanguinity, or family history of note. Physical examination revealed normal development and growth, no fever, no lymphadenopathy, no hepatomegaly and splenomegaly. A complete blood count (CBC) revealed normochromic normocytic anaemia, thrombocytopenia, and leucopenia. His blood biochemistry showed hepatic cytolysis, and hepato-cellular insufficiency. Wilson’s disease was suspected because of the combination of the impaired liver function, hemolytic anaemia, and normal alkaline phosphatase levels. Serum ceruloplasmin and copper levels were decreased, while urinary copper was elevated confirming the diagnosis of Wilson’s disease. There was no neurological or ophthalmologic involvement. Family investigation revealed Wilson's disease with cirrhosis in a 9-year-old brother. The onset of nephrotic syndrome and the presence of inflammatory syndrome cannot be explained by Wilson’s disease. The kidney biopsy histopathology revealed nephritis lupus class II (WHO classification). Subsequent serum analysis also revealed positive native anti-DNA and anti-PCNA antibodies verified on a second sample. Based on all the findings, the final diagnosis for this patient was Wilson’s disease combined with SLE. We started therapy with bolus of corticosteroids and Cyclophosphamide, relayed by Mycophenolate Moftil and hydroxychloroquine Cooper chelation has also been initiated. Improvement in renal and even hepatic damage was noted. Unfortunately, after two years, the patient presented abnormal movements with dysarthria. Brain MRI showed abnormal signals of the basal ganglia consistent with neurological damage in Wilson's disease. Discussion concomitant SLE and WD without penicillamine treatment is rare (7 cases reported in the literature with 3 children). To our knowledge, this is the first report of an association between Wilson's disease and SLE in male case. For our patient, SLE and Wilson’s disease were diagnosed simultaneously as 4 described cases. Wilson’s disease was first suspected due to unexplained impaired liver function with hemolytic anaemia. Copper Tests confirming the diagnosis. At that time, there was no neurological or ophthalmological impairment. For this patient, the worsening of the hematological involvement (pancytopenia) in an inflammatory context, with installation of a nephrotic syndrome cannot be explained by Wilson's disease. SLE was evoked despite the fact that it was a child and male. The PBR as well as the immunological workup were in favor of SLE disease. Treatment of SLE improved symptoms but later chelation could not prevent the usual neurologic complication of Wilson’s disease at this age. The neurological involvement appeared at the age of 14 as described in the literature with the common sign dysathria, followed by the installation of abnormal movements due to the impairment of the basal ganglia objectived by MRI. Conclusion Wilson’s disease and SLE not induced by penicillamine can co-exist. As there is no pathophysiological explanation, it’s probably a simple fortuitous association.


Background
Wilson's disease (WD) is a rare, recessively inherited disorder of copper metabolism with its accumulation in multiple organs particularly in the liver and brain. Systematic lupus erythematosus (SLE) is an autoimmune disease like Wilson's disease, involves multiple organs and systems. The combination of Wilson's disease and systemic lupus erythematosus (SLE) is not usual apart from iatrogenism. Objectives we present a pediatric case of concurrent Wilson's disease and primary SLE not induced by penicillamine. After extensive research in the literature, this is the only male case described so far. The other seven cases reported are female. Case presentation A previously well 12-year-old boy was admitted to University Hospital Center of Batna (Algeria) with acute haemolysis (pallor, subictereus, and red urine). There was no consanguinity, or family history of note. Physical examination revealed normal development and growth, no fever, no lymphadenopathy, no hepatomegaly and splenomegaly. A complete blood count (CBC) revealed normochromic normocytic anaemia, thrombocytopenia, and leucopenia. His blood biochemistry showed hepatic cytolysis, and hepato-cellular insufficiency. Wilson's disease was suspected because of the combination of the impaired liver function, hemolytic anaemia, and normal alkaline phosphatase levels. Serum ceruloplasmin and copper levels were decreased, while urinary copper was elevated confirming the diagnosis of Wilson's disease. There was no neurological or ophthalmologic involvement. Family investigation revealed Wilson's disease with cirrhosis in a 9year-old brother. The onset of nephrotic syndrome and the presence of inflammatory syndrome cannot be explained by Wilson's disease. The kidney biopsy histopathology revealed nephritis lupus class II (WHO classification). Subsequent serum analysis also revealed positive native anti-DNA and anti-PCNA antibodies verified on a second sample. Based on all the findings, the final diagnosis for this patient was Wilson's disease combined with SLE. We started therapy with bolus of corticosteroids and Cyclophosphamide, relayed by Mycophenolate Moftil and hydroxychloroquine Cooper chelation has also been initiated. Improvement in renal and even hepatic damage was noted. Unfortunately, after two years, the patient presented abnormal movements with dysarthria. Brain MRI showed abnormal signals of the basal ganglia consistent with neurological damage in Wilson's disease. Discussion concomitant SLE and WD without penicillamine treatment is rare (7 cases reported in the literature with 3 children). To our knowledge, this is the first report of an association between Wilson's disease and SLE in male case. For our patient, SLE and Wilson's disease were diagnosed simultaneously as 4 described cases. Wilson's disease was first suspected due to unexplained impaired liver function with hemolytic anaemia. Copper Tests confirming the diagnosis. At that time, there was no neurological or ophthalmological impairment. For this patient, the worsening of the hematological involvement (pancytopenia) in an inflammatory context, with installation of a nephrotic syndrome cannot be explained by Wilson's disease. SLE was evoked despite the fact that it was a child and male. The PBR as well as the immunological workup were in favor of SLE disease. Treatment of SLE improved symptoms but later chelation could not prevent the usual neurologic complication of Wilson's disease at this age. The neurological involvement appeared at the age of 14 as described in the literature with the common sign dysathria, followed by the installation of abnormal movements due to the impairment of the basal ganglia objectived by MRI.

Conclusion
Wilson's disease and SLE not induced by penicillamine can co-exist. As there is no pathophysiological explanation, it's probably a simple fortuitous association.

Athul Kooliyath and Angela Migowa
The Aga Khan University, Nairobi

Background
Methotrexate is an antimetabolite commonly used as a chemotherapeutic and as a steroid sparing agent in multiple rheumatologic conditions. The common side effects are well documented and usually seen in patients receiving high dose therapy and hence more commonly seen in oncology. Here, we discuss a case on methotrexate toxicity in a patient being treated for Takayasu arteritis.

Methods
This was a retrospective case review Results A seventeen-year-old was seen in the rheumatology service with a diagnosis of Takayasu arteritis after being initially worked up due to hypertension. Methotrexate therapy was started at an initial dose of 25 mg to be taken weekly. She was later seen in the pediatric outpatient unit 10 days post initiation of therapy with a history of inability to feed due to oral sores and severe abdominal pain. She also complained of odynophagia and hence had poor oral intake. On further history, it was noted that the patient was taking the medication on a daily basis as opposed to the prescribed weekly regimen. On exam, she was noted to have extensive ulceration of her buccal mucosa, gingiva and tongue. She was also found to have severe epigastric tenderness. Her genital regions were however spared. A diagnosis of methotrexate toxicity was made and she was admitted to the high dependency unit for management. Methotrexate was immediately discontinued and a hyper hydration regimen was initiated with intravenous fluids (125 ml/m 2 /h). Her pain was managed with an intravenous morphine infusion. Particular care was taken to avoid drugs such as proton pump inhibitors (PPIs), non-steroidal antiinflammatory drugs (NSAIDs) and Sulphur containing drugs. A rescue was initiated with 15 mg/m 2 of folinic acid given 6 hourly. The patient made a full recovery and was discharged 4 days later.

Discussion and Conclusions
Methotrexate is a drug with varied and severe adverse effects. Toxicity with methotrexate affects multiple systems and can cause end organ damage. It is therefore of paramount importance to recognize toxicity early and manage appropriately before onset of end organ damage. The above patient was risk of hepatotoxicity, renal toxicity, Neurologic toxicity, methotrexate induced lung injury, hematologic toxicity and hypersensitivity. She developed mucositis as a result of the medication. Enhancing renal elimination of the drug is at the core of management. This can be done with hyperhydration, alkalinisation of urine and avoiding drugs that slow elimination of methotrexate such as PPIs, NSAIDs, tyrosine kinase inhibitors, sulfa drugs and penicillin like drugs. Once end organ damage is established, therapy is supportive and highly dependent on the organ systems involved and the extent of injury. It is necessary for clinicians to be well versed with the adverse effects expected with methotrexate as evidenced by this case for prompt diagnosis and sound management. It is also vital to counsel patients and parents about the medication-correct dosage and timing, expected adverse effects and when to seek medical attention. Background Childhood-onset systemic lupus erythematosus (c-SLE) is the prototype of a multisystem, inflammatory, heterogeneous autoimmune condition, characterized by simultaneous or sequential organ involvement. Compared with the adult-onset form, c-SLE have a worse prognosis.

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